11-62884644-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013251.3(SLC3A2):c.772T>G(p.Phe258Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: SLC3A2 NM_001013251.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.878

Genes affected

SLC3A2 (HGNC:11026): (solute carrier family 3 member 2) This gene is a member of the solute carrier family and encodes a cell surface, transmembrane protein. The protein exists as the heavy chain of a heterodimer, covalently bound through di-sulfide bonds to one of several possible light chains. The encoded transporter plays a role in regulation of intracellular calcium levels and transports L-type amino acids. Alternatively spliced transcript variants, encoding different isoforms, have been characterized. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22673592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC3A2	NM_001013251.3	c.772T>G	p.Phe258Val	missense_variant	5/9	ENST00000338663.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC3A2	ENST00000338663.12	c.772T>G	p.Phe258Val	missense_variant	5/9	1	NM_001013251.3	P2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 19, 2022

The c.1078T>G (p.F360V) alteration is located in exon 8 (coding exon 8) of the SLC3A2 gene. This alteration results from a T to G substitution at nucleotide position 1078, causing the phenylalanine (F) at amino acid position 360 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
Cadd	Benign	15
Dann	Benign	0.96
DEOGEN2	Benign	0.24	T;.;.;.;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.82	T;T;T;T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.23	T;T;T;T;T
MetaSVM	Uncertain	0.65	D
MutationAssessor	Uncertain	2.1	M;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.2	N;N;N;N;N
REVEL	Uncertain	0.47
Sift	Benign	0.17	T;T;T;T;T
Sift4G	Benign	0.46	T;T;T;T;T
Polyphen		0.89	P;.;B;P;P
Vest4		0.18
MutPred		0.72		Gain of helix (P = 0.0696);.;.;.;.;
MVP		0.82
MPC		0.67
ClinPred		0.40	T
GERP RS		-1.5
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.3
Varity_R		0.19
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-62652116;